NOTICE: Applications submitted in response to this
Funding Opportunity Announcement (FOA) for Federal assistance must be submitted
electronically through Grants.gov (http://www.grants.gov) using the SF424 Research and Related (R&R) forms and the SF424
(R&R) Application Guide.

APPLICATIONS MAY NOT
BE SUBMITTED IN PAPER FORMAT.

This FOA must be read
in conjunction with the application guidelines included with this announcement
in Grants.gov/Apply
for Grants (hereafter called Grants.gov/Apply).

A registration process
is necessary before submission and applicants are highly encouraged to start
the process at least four (4) weeks prior to the grant submission date. See Section IV.

Purpose.This FOA issued by NCRR (NIH) and ORI encourages research grant applications from
institutions/organizations that propose to study research integrity as it
relates to collaborative interactions and/or activities. The R21
exploratory/developmental mechanism will be used to foster research where there are few published data and where
problem areas that would benefit from further investigation could be
identified. Applications must address the influence of collaborative
interactions and/or activities on research integrity in at least one of the following areas that are of particular interest
to the ORI and NIH: the clarification of community norms and standards,
the effectiveness of self-regulation, the societal, organizational, group,
or individual factors that affect integrity in research, both positively and negatively, or the impacts of
non-adherence to accepted codes of conduct. The proposed project must
challenge existing paradigms, be developed around an innovative hypothesis
or address critical barriers to progress in understanding the multiple factors that underlie deviation from
integrity in collaborative research. Proposals must have clear relevance
to biomedical, behavioral health sciences, or health services research.
Applicants are encouraged to take into consideration problems or issues that have relevance to the specific
interests of ORI or NIH Institutes and Centers.

Mechanism of Support. This FOA will utilize the R21 grant
mechanism.

Funds Available and Anticipated Number of Awards.Funding for FY2009 is anticipated
to be $850,000 in total costs to support two to three new R21 awards.
Awards issued under this FOA are contingent upon the availability of funds
and the submission of a sufficient number of meritorious applications.

Budget and Project Period.The total project period for an application submitted
in response to this funding opportunity may not exceed two years. Direct
costs are limited to $275,000 over a two-year period, with no more than
$200,000 in direct costs allowed in any single year.

Application Research Plan Component Length: The R21 application Research Plan component of the PHS398 (Items
2-5) may not exceed 15 pages, including tables, graphs, figures, diagrams,
and charts. For information on NIH Exploratory/Developmental Research
Grant Award (R21). See
also http://grants.nih.gov/grants/funding/funding_program.htm.

Eligible Project Directors/Principal
Investigators (PDs/PIs). Individuals with the
skills, knowledge, and resources necessary to carry out the proposed
research are invited to work with their institution/ organization to develop
an application for support. Individuals from underrepresented racial and
ethnic groups as well as individuals with disabilities are always
encouraged to apply for NIH support.

Number of PDs/PIs. More than one PD/PI
(i.e., multiple PDs/PIs) may be designated on the application.

Number
of Applications. Applicants may submit more than one application,
provided each application is scientifically distinct.

Resubmissions.Resubmission of applications will not be accepted.

o Renewals.Exploratory/developmental grant support is for new projects only; renewal
(formerly “competing continuation”) applications will not be accepted.

Collaborations greatly
expand the possibilities in research.
Interdisciplinary collaborations are encouraged across health-related
investigations; however norms and conventions differ among fields, disciplines,
cultures, and countries. These differences present unique challenges in
maintaining integrity in collaborative research.
Published research data are needed in the following significant areas:

standards that guide responsible conduct in collaborative
research, how they are established, and the extent to which the collaborating
researchers routinely adhere to these standards

effectiveness of professional self-regulation in
collaborative research

the factors in collaborative research that influence
students, researchers and research institutions to adhere to or deviate from
their norms of integrity in research and how these
factors can be reinforced or modified to promote responsible practices

the economic, policy and intellectual impacts of
collaborative research behaviors that fail to adhere to rules, regulations,
guidelines, and commonly accepted professional codes
or norms

Purpose

The purpose of this
exploratory/developmental grant program is to foster research on research
integrity in areas of collaborative research that have little published data.
The proposed project must challenge existing paradigms,
be developed around an innovative hypothesis or address critical barriers to
progress in understanding the multiple factors that underlie deviation from
integrity in collaborative research. The sponsoring agencies are particularly
interested in research focused on integrity in
collaborative research that will provide clear evidence (rates of occurrence
and impacts) of problem areas in community standards, self-regulation, practice
norms, and non-adherence to accepted codes of conduct. The application must address the societal, organizational, group, or
individual factors that affect integrity in collaborative research, both
positively and negatively. Applications must have relevance to health sciences
research including, for example, those biomedical,
behavioral health sciences, or health services research areas having particular
positive or negative collaborative research integrity issues. Applicants must
address problems or issues that have relevance to the specific interests of ORI
or NIH Institutes and Centers.

For the purposes of
this FOA, “collaborative research” includes the societal, organizational,
group, and individual aspects of data acquisition and interpretation.
"Integrity" is understood as the use of honest and verifiable methods
in proposing, performing, and evaluating research and
reporting research results with particular attention to adherence to rules,
regulations, guidelines, and commonly accepted professional codes or norms.
“Integrity in collaborative research” requires adhering
to the principles of integrity and responsible collaborative research
practices. For additional information, refer to:
http://ori.hhs.gov/research/potential_research_topics.shtml

This program will use
the R21 mechanism. Applications submitted under this
mechanism must be developmental or exploratory and novel. These studies must
break new ground or extend previous discoveries toward new directions or
applications. R21 proposals must describe projects that are distinct from those
supported through the traditional NIH R01 mechanism.
For example, long-term projects, or projects designed to increase knowledge in
a well-established area, will not be considered for R21 awards.

Although pilot data are
not required for submission of the R21 application, it is expected that feasibility, based on a strong research plan, will be
established in the application. Data resulting from funded applications will be
useful for future grant applications and the resulting publications will aid in
policymaking decisions that will help promote
integrity in PHS funded research. The participating agencies are especially
interested in quantifiable information that is relevant to particular
PHS-supported research communities and/or research interests. Projects that are
relevant to the current NIH Roadmap Initiatives (New
Pathways to Discovery, Research Teams of the Future, and Re-engineering the
Clinical Research Enterprise: http://nihroadmap.nih.gov ) are also encouraged.

Proposals focused on
normative ethical analysis or biomedical ethics
issues will not be considered. Applicants with these interests should consider
applying for “Research on Ethical Issues in Human Subjects Research,” PA-06-367
(R03), PA-06-368 (R21), or PA-06-369 (R01).

The NCRR and NICHD are particularly interested in research
on issues that would impact on clinical and translational collaborative
research.

The areas of research detailed below are of special
interest to ORI and participating NIH Institutes:

1. Factors that enhance
or undermine integrity in collaborative research. Multiple factors influence
research integrity. The participating Institutes and Agencies are interested in exploratory studies that identify the principal
factors impacting the maintenance of high standards for research integrity
within collaborations. Studies proposed in this area should not only explore
what these factors are but also how they can be
influenced or changed through education, institutional policies, or research
incentives. There is particular interest in developmental or exploratory
studies that identify specific factors for enhancing integrity in collaborative
research with respect to:

responsible conduct of research (RCR) education for all
involved in a collaboration

approaches to mentoring that is focused on maintaining
integrity in collaborative research

conflicts of interest, particularly those that involve financial gain for some or all collaborators

the effectiveness of research regulations on collaborative
interactions and research activity

the collaborative organization of individual laboratories
and clinical research settings

the organization of large
research collaborations (clinical trials, multi-site research, international
research)

2. Standards for
responsible conduct: The standards for responsible conduct in research are
complex, not always apparent, and readily influenced by external pressures such as those exerted by collaboration. While some
standards are clearly defined and require adherence (e.g., Federal regulations
for human and animal research or for handling misconduct), other clearly
described standards have no compelling authority
(e.g., Federal guidelines and professional codes of conduct). Alternatively,
many are based on customs rather than clearly defined standards and these can
vary from field to field or research setting to research setting (e.g.,
standards for designing experiments; standards for
recording, storing, interpreting and reporting data; or standards for assigning
authorship). Integrity in collaborative research is particularly impacted by
the lack of clearly defined standards and by variability across scientific areas. The participating Institutes and Agencies are
interested in developmental or exploratory studies focused on the:

formulation of standards for responsible conduct in
collaborative research

endorsement of research integrity practices in collaborations

In proposing studies in
this area, researchers should pay attention to and clearly distinguish between
ideal practices that are recommended and actual practices that are routinely
accepted as responsible. There is particular interest in developmental or exploratory studies that focus on the standards for
responsible conduct within collaborative research for:

collaborations with researchers and laboratories distant from the investigators, particularly with
regard to clinical trials and international research

collaboration practices that lead to the creation of
federated research databases

mentoring and mentor training with regard to maintaining integrity during collaborative research

3. Self-regulation.
Self-regulation plays a vital role in maintaining integrity in research and the
reliability of the research record. Self-regulation is particularly important
to maintenance of integrity during collaborative
research activities and interactions. Even in areas that are subject to Federal
and local regulation (e.g., misconduct policies), regulators and administrators
rely heavily on the research community to follow the rules and to report
problems that they observe. The participating
Institutes and Agencies are interested in identifying the role of
self-regulation in the context of different collaborative research areas and
the effectiveness of self-regulation in maintaining research integrity. Studies proposed in this area should explore the:

impact on self-regulation of variations from ideal in real
practice settings involving collaborative research

investigator’s acceptance of self-regulation within the
context of collaborative research

effectiveness of self-regulation
during collaborative research

There is particular
interest in self- regulation within the context of collaborative research as it
pertains to the:

response to and prevention of research misconduct and
questionable research practices

response to prevention of inadvertent and careless errors

practice of introducing amendments and corrections to
online full-text and research databases

promotion of responsible mentoring and its impact on
collaborative laboratory practices

4. Economic, policy,
and scientific impacts. The goals of NIH-supported research are to advance our
understanding of biological systems, improve the control of disease, and
enhance health. This goal is compromised by behaviors that contravene rules,
regulations, guidelines, and commonly accepted
professional codes or norms. The participating Institutes and Agencies are
interested in identifying the economic, policy and scientific impacts of
research misconduct and questionable research practices within the context of collaborative research interactions and
activities. Developmental or exploratory studies of integrity in collaborative
research are encouraged where they provide data and guidance with regard to
interpreting scientific results on the:

actual dollar costs of duplicate publication, the failure to share data in a timely manner, bias
resulting from conflict of interest, and other questionable practices that slow
the progress of science and waste research time and funding

identification and extent of misconduct and questionable research practices that compromise the reliability of the
scientific record

cause and degree that misconduct and questionable research
practices improperly inform public policy or health decisions

The evolution and
vitality of the biomedical sciences require a
constant infusion of new ideas, techniques, and points of view. These may
differ substantially from current thinking or practice and may not yet be
supported by substantial preliminary data. By using the R21 mechanism, the NIH
seeks to foster the introduction of novel scientific
ideas, model systems, tools, agents, targets, and technologies that have the
potential to substantially advance biomedical research.

The R21 mechanism is
intended to encourage new exploratory and developmental research projects. For example, such projects could assess the
feasibility of a novel area of investigation or a new experimental system that
has the potential to enhance health-related research. Another example could
include the unique and innovative use of an existing
methodology to explore a new scientific area. These studies may involve
considerable risk but may lead to a breakthrough in a particular area, or to
the development of novel techniques, agents, methodologies, models, or
applications that could have a major impact on a
field of biomedical, behavioral, or clinical research.

Applications for R21
awards should describe projects distinct from those supported through the
traditional R01 mechanism. For example, long-term projects, or projects
designed to increase knowledge in a well-established
area, will not be considered for R21 awards. Applications submitted under this
mechanism should be exploratory and novel. These studies should break new
ground or extend previous discoveries toward new directions or applications.

This FOA will use theR21 award mechanism. The Project Director/Principal Investigator (PD/PI) will
be solely responsible for planning, directing, and executing the proposed project.

This FOA uses “Just-in-Time” information concepts (see SF424 (R&R)
Application Guide). It also uses the modular as well as the
non-modular budget formats (seehttp://grants.nih.gov/grants/funding/modular/modular.htm).
Specifically, a U.S. organization submitting an application with direct costs
in each year of $250,000 or less (excluding consortium Facilities and
Administrative [F&A] costs) must use the PHS398 Modular Budget component.

U.S. applicants requesting more than
$250,000 in annual direct costs and all foreign applicants must complete and
submit budget requests using the Research & Related Budget component.

2.
Funds Available

The
participating organization(s) ORI, NCRR and NICHD intend to commit
approximately $850,000 in FY2009 to fund 2-3 applications.

Although
the size of award may vary with the scope of research proposed, it is expected
that applications will stay within the budgetary guidelines for an
exploratory/developmental project; direct costs are limited to $275,000 over an
R21 two-year period, with no more than $200,000 in direct costs allowed in any
single year. Applicants may request direct costs in $25,000 modules, up to the
total direct costs limitation of $275,000 for the combined two-year award
period.

Because
the nature and scope of the proposed research will vary from application to
application, it is anticipated that the size and duration of each award will
also vary. Although the financial plans of the IC(s) provide support for this
program, awards pursuant to this funding opportunity are contingent upon the
availability of funds.

Facilities
and Administrative (F&A) costs requested by consortium participants are not
included in the direct cost limitation. See NOT-OD-05-004.

The decision of whether to
apply for a grant with a single PD/PI or multiple PDs/PIs grant is the
responsibility of the investigators and applicant organizations and should be
determined by the scientific goals of the project. Applications for grants with
multiple PDs/PIs will require additional information, as outlined in the
instructions below. The NIH review criteria for approach, investigators, and environment
have been modified to accommodate applications involving either a single PD/PI
or multiple PDs/PIs. When considering the multiple PD/PI option, please be
aware that the structure and governance of the PD/PI leadership team as well as
the knowledge, skills and experience of the individual PDs/PIs will be factored
into the assessment of the overall scientific merit of the application.
Multiple PDs/PIs on a project share the authority and responsibility for
leading and directing the project, intellectually and logistically. Each
PD/PI is responsible and accountable to the grantee organization, or, as
appropriate, to a collaborating organization, for the proper conduct of the
project or program, including the submission of required reports. For further
information on multiple PDs/PIs, please seehttp://grants.nih.gov/grants/multi_pi.

Applicants are not permitted to submit a
resubmission application in response to this FOA.

Renewal
applications are not permitted in response to this FOA

Applicants may submit more than one application, provided
each application is scientifically distinct.

Section IV. Application and Submission Information

To
download a SF424 (R&R) Application Package and SF424 (R&R) Application
Guide for completing the SF424 (R&R) forms for this FOA, use the “Apply for
Grant Electronically” button in this FOA or link to http://www.grants.gov/Apply/ and follow
the directions provided on that Web site.

A one-time registration is required for institutions/organizations at both:

· The individual(s) designated as
PDs/PIs on the application must be registered also in the NIH eRA Commons. In the case of multiple PDs/PIs, all PDs/PIs must be registered and be assigned
the PI role in the eRA Commons prior to the submission of the application.

Each PD/PI must
hold a PD/PI account in the Commons. Applicants should not share a Commons account for both an Authorized Organization
Representative/Signing Official (AOR/SO) role and a PD/PI role; however, if they have both a
PD/PI role and an NIH Internet Assisted Review (IAR) role, both roles should
exist under one Commons account.

When multiple PDs/PIs are
proposed, all PDs/PIs at the applicant organization must be affiliated with
that organization. PDs/PIs located at another institution need not be
affiliated with the applicant organization, but must be affiliated with their
own organization to be able to access the Commons.

This registration/affiliation must
be done by the AOR/SO or his/her designee who is already registered in the Commons.

Both the PDs/PI(s) and
AOR/SO need separate accounts in the NIH eRA Commons since both are authorized
to view the application image.

Note that if a PD/PI is
also an NIH peer reviewer with an Individual DUNS and CCR registration, that
particular DUNS number and CCR registration are for the individual reviewer
only. These are different than any DUNS number and CCR registration used by an
applicant organization. Individual DUNS and CCR registration should be used
only for the purposes of personal reimbursement and should not be used on any
grant applications submitted to the Federal Government.

Several of the steps of
the registration process could take four weeks or more. Therefore, applicants
should immediately check with their business official to determine whether
their organization/institution is already registered in both Grants.gov and the Commons. The NIH will accept
electronic applications only from organizations that have completed all
necessary registrations.

1. Request Application Information

Applicants must
download the SF424 (R&R) application forms and the SF424 (R&R)
Application Guide for this FOA through Grants.gov/Apply.

Note:
Only the forms package directly attached to a specific FOA can be used. You
will not be able to use any other SF424 (R&R) forms (e.g., sample forms,
forms from another FOA), although some of the "Attachment" files may
be useable for more than one FOA.

Prepare all
applications using the SF424 (R&R) application forms and in accordance with
the SF424 (R&R) Application Guide for this FOA
through Grants.gov/Apply.

The SF424 (R&R)
Application Guide is critical to submitting a complete and accurate application
to NIH. Some fields within the SF424 (R&R) application components, although
not marked as mandatory, are required by NIH (e.g., the “Credential” log-in
field of the “Research & Related Senior/Key Person Profile” component must
contain the PD/PI’s assigned eRA Commons User ID). Agency-specific
instructions for such fields are clearly identified in the Application Guide.
For additional information, see “Frequently Asked Questions – Application
Guide, Electronic
Submission of Grant Applications.”

The SF424 (R&R)
application has several components. Some components are required, others are
optional. The forms package associated with this FOA in Grants.gov/APPLYincludes all applicable components, required and optional. A completed
application in response to this FOA includes the data in the following
components:

Proposed research should provide special opportunities
for furthering research programs through the use of unusual talent, resources,
populations, or environmental conditions in other countries that are not
readily available in the United States (U.S.) or that augment existing U.S. resources.

SPECIAL INSTRUCTIONS

Applications with
Multiple PDs/PIs

When
multiple PDs/PIs are proposed, NIH requires one PD/PI to be designated as the
"Contact” PI, who will be responsible for all communication between the
PDs/PIs and the NIH, for assembling the application materials outlined below,
and for coordinating progress reports for the project. The contact PD/PI must
meet all eligibility requirements for PD/PI status in the same way as other
PDs/PIs, but has no other special roles or responsibilities within the project team
beyond those mentioned above.

Information
for the Contact PD/PI should be entered in item 15 of the SF424 (R&R) Cover
component. All other PDs/PIs should be listed in the Research &
Related Senior/Key Person component and assigned the project role of
“PD/PI.” Please remember that all PDs/PIs must be registered in the eRA Commons prior to application submission. The Commons ID of each PD/PI must be included in the
“Credential” field of the Research & Related Senior/Key Person
component. Failure to include this data field will cause the application
to be rejected.

All projects
proposing Multiple PDs/PIs will be required to include a new section describing
the leadership plan approach for
the proposed project.

Multiple
PD/PI Leadership Plan: For applications designating multiple PDs/PIs, a new
section of the research plan, entitled “Multiple PD/PI Leadership Plan”
[Section 14 of the Research Plan Component in the SF424 (R&R)], must be
included. A rationale for choosing a multiple PD/PI approach should be described.
The governance and organizational structure of the leadership team and the
research project should be described, and should include communication plans,
process for making decisions on scientific direction, and procedures for
resolving conflicts. The roles and administrative, technical, and
scientific responsibilities for the project or program should be delineated for
the PDs/PIs and other collaborators.

If
budget allocation is planned, the distribution of resources to specific
components of the project or the individual PDs/PIs should be delineated in the
Leadership Plan. In the event of an award, the requested allocations may be
reflected in a footnote on the Notice of Award (NoA).

Applications Involving a
Single Institution

When all PDs/PIs are
within a single institution, follow the instructions contained in the SF424
(R&R) Application Guide.

Applications Involving
Multiple Institutions

When
multiple institutions are involved, one institution must be designated as the
prime institution and funding for the other institution(s) must be requested
via a subcontract to be administered by the prime institution. When submitting
a detailed budget, the prime institution should submit its budget using the
Research & Related Budget component. All other institutions should
have their individual budgets attached separately to the Research & Related
Subaward Budget Attachment(s) Form. See Section 4.8 of the SF424 (R&R)
Application Guide for further instruction regarding the use of the subaward
budget form.

When
submitting a modular budget, the prime institution completes the PHS398 Modular
Budget component only. Information concerning the consortium/subcontract
budget is provided in the budget justification. Separate budgets for each
consortium/subcontract grantee are not required when using the Modular budget
format. See Section 5.4 of the Application Guide for further instruction
regarding the use of the PHS398 Modular Budget component.

Prospective
applicants are asked to submit a letter of intent that includes the following
information:

Descriptive title of proposed research.

Name, address, and telephone number of the
PD(s)/PI(s).

Names of other key personnel.

Participating institutions.

Number and title of this funding opportunity.

Although
a letter of intent is not required, is not binding, and does not enter into the
review of a subsequent application, the information that it contains allows IC
staff to estimate the potential review workload and plan the review.

Applications may be submitted on or after the opening date and must be
successfully received by Grants.gov no later than 5:00 p.m. local time (of the applicant
institution/organization) on the application due date(s). (See Section IV.3.A. for all dates.) If an application is not submitted by the due date(s)
and time, the application may be delayed in the review process or not reviewed.

Once an application package has been
successfully submitted through Grants.gov, any errors have been addressed, and
the assembled application has been created in the eRA Commons, the PD/PI and the Authorized Organization
Representative/Signing Official (AOR/SO) have two weekdays (Monday – Friday,
excluding Federal holidays) to view the application image to determine if any
further action is necessary.

If everything is
acceptable, no further action is necessary. The application
will automatically move forward to the Division of Receipt and Referral in
the Center for Scientific Review for processing after two weekdays,
excluding Federal holidays.

Prior to the submission
deadline, the AOR/SO can “Reject” the assembled application and submit a
changed/corrected application within the two-day viewing window. This
option should be used if it is determined that some part of the
application was lost or did not transfer correctly during the submission
process, the AOR/SO will have the option to “Reject” the application and
submit a Changed/Corrected application. In these cases, please contact the eRA Help Desk to
ensure that the issues are addressed and corrected. Once rejected,
applicants should follow the instructions for correcting errors in Section
2.12, including the requirement for cover letters on late applications. The “Reject” feature should also be used if you determine that
warnings are applicable to your application and need to be addressed now.
Remember, warnings do not stop further application processing. If an
application submission results in warnings (but no errors), it will
automatically move forward after two weekdays if no action is taken. Some
warnings may need to be addressed later in the process.

If
the two-day window falls after the submission deadline, the AOR/SO will have
the option to “Reject” the application if, due to an eRA Commons or Grants.gov
system issue, the application does not correctly reflect the submitted
application package (e.g., some part of the application was lost or didn’t
transfer correctly during the submission process). The AOR/SO should first
contact the eRA Commons Helpdesk to confirm the system error, document the issue, and determine the best course
of action. NIH will not penalize the applicant for an eRA Commons or Grants.gov system issue.

If
the AOR/SO chooses to “Reject” the image after the submission deadline for a
reason other than an eRA Commons or Grants.gov system failure, a
changed/corrected application still can be submitted, but it will be subject to
the NIH
late policy guidelines and may not be accepted. The reason for this delay
should be explained in the cover letter attachment.

Both
the AOR/SO and PD/PI will receive e-mail notifications when the application is
rejected or the application automatically moves forward in the process after
two weekdays.

Upon receipt, applications will be evaluated for
completeness by the CSR and responsiveness by the IC. Incomplete and
non-responsive applications will not be reviewed.

There
will be an acknowledgement of receipt of applications from Grants.gov and the Commons. The submitting AOR/SO
receives the Grants.gov acknowledgments. The AOR/SO and the PI receive Commons acknowledgments. Information related to the assignment of an application to a Scientific
Review Group is also in the Commons.

Note: Since email can be
unreliable, it is the responsibility of the applicant to check periodically on
the application status in the Commons.

The
NIH will not accept any application in response to this funding opportunity
that is essentially the same as one currently pending initial review, unless
the applicant withdraws the pending application. However, when a previously
unfunded application, originally submitted as an investigator-initiated
application, is to be submitted in response to a funding opportunity, it is to
be prepared as a NEW application. That is, the application for the funding
opportunity must not include an “Introduction” describing the changes and
improvements made, and the text must not be marked to indicate the changes from
the previous unfunded version of the application.

All NIH awards are
subject to the terms and conditions, cost principles, and other considerations
described in the NIH Grants Policy Statement.

Pre-award costs are
allowable. A grantee may, at its own risk and without NIH prior approval, incur
obligations and expenditures to cover costs up to 90 days before the beginning
date of the initial budget period of a new or renewal award if such costs: 1)
are necessary to conduct the project, and 2) would be allowable under the
grant, if awarded, without NIH prior approval. If specific expenditures would
otherwise require prior approval, the grantee must obtain NIH approval before
incurring the cost. NIH prior approval is required for any costs to be incurred
more than 90 days before the beginning date of the initial budget period of a
new or renewal award.

The incurrence of pre-award costs in anticipation of a
competing or non-competing award imposes no obligation on NIH either to make
the award or to increase the amount of the approved budget if an award is made
for less than the amount anticipated and is inadequate to cover the pre-award
costs incurred. NIH expects the grantee to be fully aware that pre-award costs
result in borrowing against future support and that such borrowing must not
impair the grantee's ability to accomplish the project objectives in the
approved time frame or in any way adversely affect the conduct of the project
(see theNIH
Grants Policy Statement).

The
applicant organization must include its DUNS number in its Organization Profile
in the eRA Commons. This DUNS number must match the DUNS number provided at CCR
registration with Grants.gov. For
additional information, see “Frequently Asked Questions – Application Guide, Electronic
Submission of Grant Applications.”

PHS398
Research Plan Component Sections

Page
limitations of the PHS398 Research Plan component must be followed as outlined
in the SF424 (R&R) Application Guide. While each section of the Research
Plan component needs to be uploaded separately as a PDF attachment, applicants
are encouraged to construct the Research Plan component as a single document,
separating sections into distinct PDF attachments just before uploading the
files. This approach will enable applicants to better monitor formatting
requirements such as page limits. All attachments must be provided to NIH in
PDF format, filenames must be included with no spaces or special characters,
and a .pdf extension must be used.

All
application instructions outlined in the SF424 (R&R) Application Guide are
to be followed, incorporating "Just-in-Time" information concepts,
and with the following requirements for R21 applications:

R21 applications will use the modular as well as the non-modular budget formats and
"Just-in-Time" information concepts, with direct costs requested
in $25,000 modules, up to the total direct costs limitation of $275,000 over
an R21 two-year period. No more than $200,000 in direct costs will be
allowed in any single year. All foreign
applicants must complete and submit budget requests using the Research
& Related Budget component.

Items 2-5 of the Research Plan component of the R21 application may
not exceed 15 pages, including tables, graphs, figures, diagrams, and
charts.

Introduction (required for a resubmission application) is limited
to one page.

Do not use the Appendix to circumvent the page limitations of
the Research Plan component. An application that does not comply with the
required page limitations may be delayed in the review process.

Resource Sharing
Plan(s)

NIH
considers the sharing of unique research resources developed through
NIH-sponsored research an important means to enhance the value and further the
advancement of the research. When resources have been developed with NIH funds
and the associated research findings published or provided to NIH, it is
important that they be made readily available for research purposes to
qualified individuals within the scientific community. If the final data/resources are not amenable to sharing,
this must be explained in the Resource Sharing section of the application (see http://grants.nih.gov/grants/policy/data_sharing/data_sharing_faqs.htm.)

(b) Sharing Model Organisms:
Regardless of the amount requested, all applications where the development of
model organisms is anticipated are expectedto include a
description of a specific plan for sharing and distributing unique model
organisms and related resources or state appropriate reasons why such sharing
is restricted or not possible (see Sharing
Model Organisms Policy, and NOT-OD-04-042.)

(c) Genome-Wide Association Studies (GWAS): Regardless of the amount requested, applicants seeking funding for a
genome-wide association study are expected to provide a plan for
submission of GWAS data to the NIH-designatedGWAS data
repository, or provide an appropriate explanation why submission to the
repository is not possible. A genome-wide association study is defined as
any study of genetic variation across the entire genome that is designed to
identify genetic associations with observable traits (e.g., blood pressure or
weight) or the presence or absence of a disease or condition. For further
information see Policy for Sharing of Data Obtained in NIH Supported or
Conducted Genome-Wide Association Studies (go to NOT-OD-07-088, and http://grants.nih.gov/grants/gwas/.)

Foreign Applications
(Non-Domestic [non-U.S.] Entities)

Indicate how the proposed project has specific
relevance to the mission and objectives of the NIH/IC and has the potential for
significantly advancing the health sciences in the United States.

Section V. Application Review Information

1.
Criteria (Update: Enhanced review criteria have been issued for the evaluation of research applications received for potential FY2010 funding and thereafter - see NOT-OD-09-025).

Only
the review criteria described below will be considered in the review process.

2.
Review and Selection Process

Applications
that are complete and responsive to this FOA will be evaluated for scientific and technical merit by an
appropriate peer review group convened by NCRR and in accordance with NIH peer review procedures (http://grants1.nih.gov/grants/peer/),
using the review criteria stated below.

As
part of the scientific peer review, all applications will:

Undergo
a selection process in which only those applications deemed to have the
highest scientific and technical merit, generally the top half of
applications under review, will be discussed and assigned a priority
score;

Receive
a written critique; and

Receive
a second level of review by an appropriate national advisory council or board.

Applications
submitted in response to this FOA will compete for available funds with all
other recommended applications submitted in response to this FOA. The following will be
considered in making funding decisions:

Scientific
merit of the proposed project as determined by peer review.

Availability
of funds.

Relevance
of the proposed project to program priorities.

The goals of NIH
supported research are to advance our understanding of biological systems, to
improve the control of disease, and to enhance health. In their written
critiques, reviewers will be asked to comment on each of the following criteria
in order to judge the likelihood that the proposed research will have a
substantial impact on the pursuit of these goals. Each of these criteria will
be addressed and considered in assigning the overall score, and weighted as
appropriate for each application. Note that an application does not need to be
strong in all categories to be judged likely to have major scientific impact
and thus deserve a meritorious priority score. For example, an investigator may
propose to carry out important work that by its nature is not innovative but is
essential to move a field forward.

Significance:Does this study address an
important problem? If the aims of the application are achieved, how will
scientific knowledge or clinical practice be advanced? What will be the effect
of these studies on the concepts, methods, technologies, treatments, services,
or preventative interventions that drive this field? Does this study identify and
address one or more of the research objectives identified in the FOA? Will the study significantly
advance these objectives? Does the study have clear relevance to biomedical, behavioral health sciences, and/or health services
research? Does the study to take into consideration problems or issues that
have relevance to specific interests of ORI or NIH Institutes and Centers? Does
the application address the societal, organizational,
group, or individual factors that affect integrity in collaborative research.

Approach:Are the
conceptual or clinical framework, design, methods, and analyses adequately
developed, well integrated, well reasoned, and appropriate to the aims of the
project? Does the applicant acknowledge potential problem areas and consider
alternative tactics? For applications designating multiple PDs/PIs, is the
leadership approach, including the designated roles and responsibilities,
governance, and organizational structure, consistent with and justified by the
aims of the project and the expertise of each of the PDs/PIs?Are the
methods clearly described? Have the researchers demonstrated feasibility of the
study? Are surveys and/or other test instruments
adequately described and appropriate to the study? Are survey cohorts
appropriate for the study and clearly identified? Can the researchers gain
access to the data and/or populations they are proposing to study? Will the
study yield data that are strong and informative.
Will the study lead to future investigations on research in collaborative
research integrity? Have the researchers fully explored prior research and
explained how their work will build on or advance that research?

For applications designating multiple PDs/PIs, does the Leadership Plan
ensure that there will be sufficient coordination and communication among the
PDs/PIs? Are the administrative plans for the management of the research
project appropriate, including plans for resolving
conflicts?

Innovation: Is the project original and
innovative? For example: Does the project challenge existing paradigms or
clinical practice; address an innovative hypothesis or critical barrier to
progress in the field? Does the project develop or employ novel concepts,
approaches, methodologies, tools, or technologies to enable investigation of the
areas of interest identified in the FOA?

Investigators:Are the PD(s)/PI(s) and other key personnel appropriately
trained and well suited to carry out this work? Is the work proposed
appropriate to the experience level of the principal investigator and other
researchers? Do(es) the PD(s)/PI(s) and investigative team bring complementary
and integrated expertise to the project (if applicable)? Is all of the needed expertise (e.g., statistical analysis, survey
methodology) available and well integrated into the project?

Environment: Do(es) the scientific environment(s) in which the
work will be done contribute to the probability of success? Do the proposed studies
benefit from unique features of the scientific environment, or subject
populations, or employ useful collaborative arrangements? Is there evidence of
institutional support? Are there environmental factors that could limit the
success of the study, such as institutional
restrictions on data gathering or institutional conflicts of interest?

2.A.
Additional Review Criteria

In addition to
the above criteria, the following items will continue to be considered in the
determination of scientific merit and the rating:

Protection
of Human Subjects from Research Risk: The involvement of human
subjects and protections from research risk relating to their participation in
the proposed research will be assessed. See the “Human Subjects Sections”
of the PHS398 Research Plan component of the SF424 (R&R).

Inclusion of Women, Minorities and Children in Research: The adequacy of
plans to include subjects from both genders, all racial and ethnic groups (and
subgroups), and children as appropriate for the scientific goals of the
research will be assessed. Plans for the recruitment and retention of subjects
will also be evaluated. See the “Human Subjects Sections” of the PHS398
Research Plan component of the SF424 (R&R)

Care and Use of Vertebrate Animals in Research: If vertebrate animals
are to be used in the project, the adequacy of the plans for their care and use
will be assessed. See the “Other Research Plan Sections” of the PHS398 Research
Plan component of the SF424 (R&R).

Biohazards: If materials or procedures are proposed that are potentially
hazardous to research personnel and/or the environment, determine if the
proposed protection is adequate.

2.B. Additional Review Considerations

Budget and
Period of Support: The reasonableness of the proposed budget and the
appropriateness of the requested period of support in relation to the proposed
research may be assessed by the reviewers. The priority score should not be
affected by the evaluation of the budget.

Applications from Foreign Organizations: Whether the project presents special opportunities
for furthering research programs through the use of unusual talent, resources,
populations, or environmental conditions in other countries that are not
readily available in the United States or that augment existing U.S. resources will be assessed.

2.C. Resource Sharing
Plan(s)

When relevant, reviewers will be instructed to comment
on the reasonableness of the following Resource Sharing Plans, or the rationale
for not sharing the following types of resources. However, reviewers will not
factor the proposed resource sharing plan(s) into the determination of
scientific merit or priority score, unless noted otherwise in the FOA. Program
staff within the IC will be responsible for monitoring the resource sharing.

A formal notification in the form of a Notice of Award
(NoA) will be provided to the applicant organization. The NoA signed by the
grants management officer is the authorizing document. Once all administrative
and programmatic issues have been resolved, the NoA will be generated via email
notification from the awarding component to the grantee business official.

Selection of an application for award is not an
authorization to begin performance. Any costs incurred before receipt of the
NoA are at the recipient's risk. These costs may be reimbursed only to the
extent considered allowable pre-award costs. See Section
IV.5., “Funding Restrictions.”

A
final progress report, invention statement, and Financial Status Report are
required when an award is relinquished when a recipient changes institutions or
when an award is terminated.

Section VII. Agency Contacts

We
encourage your inquiries concerning this funding opportunity and welcome the
opportunity to answer questions from potential applicants. Inquiries may fall
into three areas: scientific/research (program), peer review, and financial or
grants management issues:

Human Subjects
Protection:Federal regulations (45 CFR 46) require that
applications and proposals involving human subjects must be evaluated with
reference to the risks to the subjects, the adequacy of protection against
these risks, the potential benefits of the research to the subjects and others,
and the importance of the knowledge gained or to be gained (http://www.hhs.gov/ohrp/humansubjects/guidance/45cfr46.htm).

Data and Safety
Monitoring Plan:Data and safety monitoring is required for all types
of clinical trials, including physiologic toxicity and dose-finding studies
(Phase I); efficacy studies (Phase II); efficacy, effectiveness and comparative
trials (Phase III). Monitoring should be commensurate with risk. The
establishment of data and safety monitoring boards (DSMBs) is required for
multi-site clinical trials involving interventions that entail potential risks
to the participants (“NIH Policy for Data and Safety Monitoring,” NIH Guide
for Grants and Contracts, http://grants.nih.gov/grants/guide/notice-files/not98-084.html).

Sharing Research Data:Investigators submitting an NIH application seeking
$500,000 or more in direct costs in any single year are expected to include a
plan for data sharing or state why this is not possible (http://grants.nih.gov/grants/policy/data_sharing).Investigators should seek guidance from their
institutions, on issues related to institutional policies and local
institutional review board (IRB) rules, as well as local, State and Federal
laws and regulations, including the Privacy Rule. Reviewers will consider the
data sharing plan but will not factor the plan into the determination of the
scientific merit or the priority score.

Policy for Genome-Wide
Association Studies (GWAS):NIH is interested in advancing genome-wide association
studies (GWAS) to identify common genetic factors that influence health and
disease through a centralized GWAS data repository. For the purposes of this
policy, a genome-wide association study is defined as any study of genetic
variation across the entire human genome that is designed to identify genetic
associations with observable traits (such as blood pressure or weight), or the
presence or absence of a disease or condition. All applications, regardless of
the amount requested, proposing a genome-wide association study are expected to
provide a plan for submission of GWAS data to the NIH-designated GWAS data
repository, or provide an appropriate explanation why submission to the
repository is not possible. Data repository management (submission and access)
is governed by the Policy for Sharing of Data Obtained in NIH Supported or
Conducted Genome-Wide Association Studies, NIH Guide NOT-OD-07-088.
For additional information, see http://grants.nih.gov/grants/gwas/

Sharing of Model Organisms:NIH is committed to support efforts that encourage
sharing of important research resources including the sharing of model
organisms for biomedical research (see http://grants.nih.gov/grants/policy/model_organism/index.htm).
At the same time the NIH recognizes the rights of grantees and contractors to
elect and retain title to subject inventions developed with Federal funding
pursuant to the Bayh-Dole Act (see the NIH
Grants Policy Statement. Beginning October 1, 2004, all investigators
submitting an NIH application or contract proposal are expected to include in
the application/proposal a description of a specific plan for sharing and
distributing unique model organism research resources generated using NIH
funding or state why such sharing is restricted or not possible. This will
permit other researchers to benefit from the resources developed with public
funding. The inclusion of a model organism sharing plan is not subject to a
cost threshold in any year and is expected to be included in all applications
where the development of model organisms is anticipated.

Access to Research Data through the Freedom of
Information Act:The Office of Management and Budget (OMB) Circular
A-110 has been revised to provide access to research data through the Freedom
of Information Act (FOIA) under some circumstances. Data that are: (1) first
produced in a project that is supported in whole or in part with Federal funds;
and (2) cited publicly and officially by a Federal agency in support of an
action that has the force and effect of law (i.e., a regulation) may be
accessed through FOIA. It is important for applicants to understand the basic
scope of this amendment. NIH has provided guidance at http://grants.nih.gov/grants/policy/a110/a110_guidance_dec1999.htm.
Applicants may wish to place data collected under this funding opportunity in a
public archive, which can provide protections for the data and manage the
distribution for an indefinite period of time. If so, the application should
include a description of the archiving plan in the study design and include
information about this in the budget justification section of the application.
In addition, applicants should think about how to structure informed consent
statements and other human subjects procedures given the potential for wider
use of data collected under this award.

Inclusion of Women And Minorities in Clinical Research:It is the policy of the NIH that women and members of
minority groups and their sub-populations must be included in all NIH-supported
clinical research projects unless a clear and compelling justification is
provided indicating that inclusion is inappropriate with respect to the health
of the subjects or the purpose of the research. This policy results from the
NIH Revitalization Act of 1993 (Section 492B of Public Law 103-43). All
investigators proposing clinical research should read the "NIH Guidelines
for Inclusion of Women and Minorities as Subjects in Clinical Research” (http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-001.html);
a complete copy of the updated Guidelines is available at http://grants.nih.gov/grants/funding/women_min/guidelines_amended_10_2001.htm.
The amended policy incorporates: the use of an NIH definition of clinical
research; updated racial and ethnic categories in compliance with the new OMB
standards; clarification of language governing NIH-defined Phase III clinical
trials consistent with the SF424 (R&R) application; and updated roles and
responsibilities of NIH staff and the extramural community. The policy
continues to require for all NIH-defined Phase III clinical trials that: a) all
applications or proposals and/or protocols must provide a description of plans
to conduct analyses, as appropriate, to address differences by sex/gender
and/or racial/ethnic groups, including subgroups if applicable; and b)
investigators must report annual accrual and progress in conducting analyses,
as appropriate, by sex/gender and/or racial/ethnic group differences.

Inclusion of Children as Participants in Clinical Research:The NIH maintains a policy that children (i.e.,
individuals under the age of 21) must be included in all clinical research,
conducted or supported by the NIH, unless there are scientific and ethical
reasons not to include them. All investigators proposing research involving
human subjects should read the "NIH Policy and Guidelines" on the inclusion
of children as participants in research involving human subjects (http://grants.nih.gov/grants/funding/children/children.htm).

Required Education on the Protection of Human Subject Participants:NIH policy requires education on the protection of
human subject participants for all investigators submitting NIH applications
for research involving human subjects and individuals designated as key
personnel. The policy is available at http://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-039.html.

Human Embryonic Stem Cells (hESC):Criteria for Federal funding of research on hESCs can
be found at http://stemcells.nih.gov/index.asp and at http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-005.html.
Only research using hESC lines that are registered in the NIH Human Embryonic
Stem Cell Registry will be eligible for Federal funding (http://escr.nih.gov/). It is the responsibility
of the applicant to provide in the project description and elsewhere in the
application as appropriate, the official NIH identifier(s) for the hESC line(s)
to be used in the proposed research. Applications that do not provide this
information will be returned without review.

NIH Public Access Policy Requirement:
In accordance with the NIH Public Access Policy, investigators
funded by the NIH must submit or have submitted for them to the National
Library of Medicine’s PubMed Central (see http://www.pubmedcentral.nih.gov/), an electronic version of their final, peer-reviewed
manuscripts upon acceptance for publication, to be made publicly available no
later than 12 months after the official date of publication. The
NIH Public Access Policy is available at (http://grants.nih.gov/grants/guide/notice-files/NOT-OD-08-033.html).For more
information, see the Public Access webpage at http://publicaccess.nih.gov/.

Standards for Privacy of Individually Identifiable Health Information:The Department of Health and Human Services (HHS)
issued final modification to the "Standards for Privacy of Individually
Identifiable Health Information", the "Privacy Rule", on August
14, 2002. The Privacy Rule is a federal regulation under the Health Insurance
Portability and Accountability Act (HIPAA) of 1996 that governs the protection
of individually identifiable health information, and is administered and
enforced by the HHS Office for Civil Rights (OCR).

Decisions about applicability and implementation of
the Privacy Rule reside with the researcher and his/her institution. The OCR
website (http://www.hhs.gov/ocr/) provides
information on the Privacy Rule, including a complete Regulation Text and a set
of decision tools on "Am I a covered entity?" Information on the
impact of the HIPAA Privacy Rule on NIH processes involving the review,
funding, and progress monitoring of grants, cooperative agreements, and
research contracts can be found at http://grants.nih.gov/grants/guide/notice-files/NOT-OD-03-025.html.

URLs
in NIH Grant Applications or Appendices:
All applications and proposals
for NIH funding must be self-contained within specified page limitations. For
publications listed in the appendix and/or Progress report, Internet addresses
(URLs) or PubMed Central (PMC) submission identification numbers must be used
for publicly accessible on-line journal articles. Publicly accessible
on-line journal articles or PMC articles/manuscripts accepted for publication
that are directly relevant to the project may be included only as URLs or PMC submission identification numbers accompanying the full reference
in either the Bibliography & References Cited section, the Progress Report
Publication List section, or the Biographical Sketch section of the NIH grant
application. A URL or PMC submission identification number citation may be
repeated in each of these sections as appropriate. There is no limit to the
number of URLs or PMC submission identification numbers that can be cited.

Healthy People 2010:The Public Health Service (PHS) is committed to
achieving the health promotion and disease prevention objectives of
"Healthy People 2010," a PHS-led national activity for setting
priority areas. This FOA is related to one or more of the priority areas.
Potential applicants may obtain a copy of "Healthy People 2010" at http://www.health.gov/healthypeople.

Authority and Regulations:This
program is described in the Catalog of Federal Domestic Assistance at http://www.cfda.gov/ and is not subject to the
intergovernmental review requirements of Executive Order 12372. Awards are made
under the authorization of Sections 301 and 405 of the Public Health Service
Act as amended (42 USC 241 and 284) and under Federal Regulations 42 CFR Part 52 and 45 CFR Parts 74 and 92. All awards
are subject to the terms and conditions, cost principles, and other
considerations described in the NIH Grants
Policy Statement.

The PHS strongly encourages all grant recipients to
provide a smoke-free workplace and discourage the use of all tobacco products.
In addition, Public Law 103-227, the Pro-Children Act of 1994, prohibits
smoking in certain facilities (or in some cases, any portion of a facility) in
which regular or routine education, library, day care, health care, or early
childhood development services are provided to children. This is consistent
with the PHS mission to protect and advance the physical and mental health of
the American people.

Loan Repayment Programs:NIH encourages applications for educational loan
repayment from qualified health professionals who have made a commitment to
pursue a research career involving clinical, pediatric, contraception, infertility,
and health disparities related areas. The LRP is an important component of
NIH's efforts to recruit and retain the next generation of researchers by
providing the means for developing a research career unfettered by the burden
of student loan debt. Note that an NIH grant is not required for eligibility
and concurrent career award and LRP applications are encouraged. The periods of
career award and LRP award may overlap providing the LRP recipient with the
required commitment of time and effort, as LRP awardees must commit at least
50% of their time (at least 20 hours per week based on a 40 hour week) for two
years to the research. For further information, please see: http://www.lrp.nih.gov/.